Cardiac amyloidosis (amyloid cardiomyopathy) is a disease damage to the heart caused by extracellular amyloid deposition. In some cases, there may be local damage to the structures of the heart, for example, the atria; more often, heart damage is part of a systemic (generalized) pathology. Depending on the amyloid precursor protein, 36 types of amyloidosis are described, among which hereditary and acquired forms are distinguished. Cardiac amyloidosis is diagnosed 1) in the case of the amyloid infiltration in the myocardial bioptates or 2) in the case of non-cardiac amyloid deposition and the left ventricular wall thickening >12 mm without arterial hypertension and other reasons. The heart is most often affected in AL-, ATTR-, AA-, AANF-types of amyloidosis. Cardiac amyloidosis should be considered in patients with a heart failure with an unclear etiology, especially with preserved left ventricular ejection fraction, refractory to treatment, with proteinuria and CKD 4-5, in patients with idiopathic atrial fibrillation and conduction disturbances, in patients with left ventricular wall thickening of unclear etiology, low ECG voltage, unexplained arterial hypotension and pulmonary hypertension. Screening for cardiac amyloidosis should include non-invasive methods such as electrophoresis and immunofixation of blood and urine proteins, the free light lambda and kappa chains of immunoglobulins, 99Tc-DPD scintigraphy, genetic testing (if hereditary variants of amyloidosis are suspected), as well as a histological examination of biopsy samples stained with Congo red and polarizing microscopy.

Lysozyme amyloidosis is caused by an amino acid substitution in the sequence of this protein. In our study, we described a clinical case of lysozyme amyloidosis in a Russian family. In our work, we described in detail the histological changes in tissues that appeared as a result of massive deposition of amyloid aggregates that affected almost all organ systems, with the exception of the central nervous system. We determined the type of amyloidosis and mutations using mass spectrometry. Using mass spectrometry, the protein composition of tissue samples of patient 1 (autopsy material) and patient 2 (biopsy material) with histologically confirmed amyloid deposits were analyzed. Amino acid substitutions p.F21L/T88N in the lysozyme sequence were identified in both sets of samples and confirmed by sequencing of the lysozyme gene of members of this family. We have shown the inheritance of these mutations in the lysozyme gene in members of the described family. For the first time, we discovered a mutation in the first exon p.F21L of the lysozyme gene, which, together with p.T88N amino acid substitution, led to amyloidosis in members of the studied family.

Amyloidosis is a heterogeneous group of the diseases caused by the extracellular deposition of amyloid in various organs including a cardiovascular system. Aim . To study the cardiovascular damage in patients with systemic amyloidosis. Material and methods . A retrospective assessment of 38 cases of systemic amyloidosis was carried out. Diagnosis was verified by biopsy in 57,9% (27,3% of these cases were then confirmed by autopsy) and autopsy in 42,1% of patients. Congo red stain and polarized-light microscopy were used. The systemic nature of lesion was diagnosed in the positive biopsies of two or more localizations or in the positive biopsy of one localization in the combination with the clinical picture of amyloidosis at least one organ. Median (interquartile range) of age was 72,5 (64-84) years (women, 65,8%; men, 34,2%). Results . In the medical history, 81,6% of patients with systemic amyloidosis had hypertension, 52,6% — coronary artery disease, 34,2% — myocardial infarction, 36,8% — type 2 diabetes, 44,7% — atrial fibrillation, 26,3% — conduction disorders. Also 13,2% of patients had an implanted pacemaker. According to the electrocardiography, 42,3% of patients had a low QRS voltage. According to echocardiography, left ventricular (LV) hypertrophy was detected in 94,7% of patients. In addition, 31,6% of patients had signs of granular sparkling myocardial appearance, 20% — impaired local LV contractility, 77,8% — increased pulmonary artery reassure, 28,6% — LV diastolic dysfunction, 14,3% — normal diastolic function. LV ejection fraction (LVEF) was 55 (44,5-55)%. LVEF 50% — in 65% of patients. Heart failure was indicated in 71,1% of patients with systemic amyloidosis, chronic kidney disease (CKD) — in 95% of patients. The estimated glomerular filtration rate (CKD-EPI) was 21,2 (13,1-40) ml/min/1,73 m ² . Proteinuria (1,1 (0,5-3,0) g/l) was detected in 88,9% of patients. Nephrotic syndrome occurred in 27,8% of patients. Conclusion . Patients with cardiovascular lesions of unclear etiology, especially in the presence of LV wall thickening, preserved LVEF, stage 4-5 CKD and proteinuria, require screening for systemic amyloidosis.

Transthyretin amyloidosis (ATTR-amyloidosis) is a systemic disorder associated with extracellular deposition in the tissues and organs of amyloid fibrils, transthyretin-containing insoluble protein-polysaccharide complexes. The change in transthyretin conformation, leading to its destabilization and amyloidogenicity, can be acquired (wild type, ATTRwt) and hereditary due to mutations in the TTR gene (variant, ATTRv) [1, 2]. Hereditary ATTR-amyloidosis has an earlier onset and greater phenotypic diversity. The age of the manifestation, the predominant phenotype, and the prognosis are often determined by the genetic variant. To date, more than 140 variants in the TTR gene have been identified; however, most of them are described in single patients and do not have clear evidence of pathogenicity. The prospects of a new pathogenetic treatment of ATTR-amyloidosis [3], especially effective in the early stages of the disease, increases the relevance of timely diagnosis, which is challenging due to physicians' lack of awareness. This article presents a clinical case of ATTRv-amyloidosis associated with a rare pathogenic variant in the TTR gene and a newly described skin symptom. This article is a literature review.

To retrospectively analyze the results of histological examination of subcutaneous adipose tissue (SAT) biopsy specimens versus the diagnostic value of drugs manufactured by different procedures. The investigators selected and analyzed the results of biopsy studies with the simultaneous production of two different types of tissue specimens (squashed native specimens, sections from the paraffin blocks) from the abdominal SAT biopsy specimens obtained from 118 patients. In each case, the tissue specimens were stained with Congo red and examined in polarized light, concurrently using the positive control. The criterion for amyloid was the ability of congophilic deposits to birefringence with a characteristic luminescence spectrum when examined in polarized light. Compared to the sections from the paraffin blocks, the native specimens were shown to be of high diagnostic value. The advantages of different types of tissue samples made from SAT biopsy specimens were formulated. The SAT biopsy specimens are characterized by the minimal risk to a patient and by the easy way of sampling and are a frequent subject for screening biopsies. In addition to the type of amyloid, the volume, quality, and method of processing the biopsy specimen are responsible for the diagnostic value of SAT examination. The study of squashed native specimens stained with Congo red is most informative when using polarized light.

The article presents a clinical case describing a complex differential diagnosis of cardiac amyloidosis types and verification of the diagnosis of AL-amyloidosis.